In recent years, an example of one of the most important materials in regenerative medicine is collagen. Collagen is a representative protein distributed in nearly all tissues (skin, bone, cartilage, and such) in living organisms, and it is well known that it has important functions in living organisms such as maintaining the structure of biological tissues and organs by becoming a scaffold for cells. In addition, it has various physiological functions that regulate the proliferation, differentiation, and migration of cells. From these facts, it is receiving attention in the field of regenerative medicine through its use together with cells, growth factors, and such in tissue engineering medicine. So far, collagen has been used widely in the medical field as artificial organ implants (Patent Document 1), sustained drug release matrices (Patent Document 2), artificial skin (Patent Document 3), and components of biocompatible materials for use in bandage matrices for wounds and matrices for wound treatment (Patent Document 4).
Forty percent of all collagen of a living organism is in the skin, and 70% or more of the dry weight of the skin/tendon is collagen. Therefore, collagen is important in the development of artificial skin. In particular, collagen is used as a biomaterial for repairing damages in organisms. For example, it is used as a coating material for sites of skin lesion such as a burn, and healing and improvement have been reported (Non-Patent Documents 1 and 2). This means that one can have great hope for applications in the current significantly progressed field of regenerative medicine. Furthermore, it is utilized as a material useful in techniques for culturing cells and organs (Patent Documents 5 and 6). In addition, it has been pointed out that oral ingestion of collagen (type II collagen) and such may be used to suppress rheumatoid arthritis (Non-Patent Document 3). Furthermore, it has been reported that it is possible to treat by designing a gene to express a partial peptide of human collagen (type VII collagen), and introducing a low-molecular-weight collagen gene into epidermolysis bullosa cells (Non-Patent Document 4).
Many of the collagens used at present are derived from non-human mammalian species such as bovine or pigs. It is reported that when these collagens are transplanted into humans, allergic reaction occurs in approximately 3% of the patients (Non-Patent Documents 5 and 6). Furthermore, in recent years, the risk of contamination of collagen derived from non-human mammalian species with prions or pathogens has become a major problem. Therefore, a system for producing safe human-type collagens with low antigenicity and free of risk of pathogen contamination is strongly desired.
To avoid such problems, some inventors have invented a method for producing recombinant human collagen having a triple helix structure equivalent to that in a human body by infecting insect cells with a recombinant virus inserted with a cDNA encoding human collagen, and have applied for a patent (Patent Document 7). Furthermore, methods for producing human collagen using mammalian cells or yeast cells have also been devised (Patent Document 8).